Affektiivisuuden laskennallinen määritteleminen

One of the most tangled fields of research is the field of defining and modeling affective concepts, i. e. concepts regarding emotions and feelings. The subject can be approached from many disciplines. The main problem is lack of generally approved definitions. However, e.g. linguists have recently started to check the consistency of their theories with the help of computer simulations. Definitions of affective concepts are needed for performing similar simulations in behavioral sciences. In this thesis, preliminary computational definitions of affects for a simple utility-maximizing agent are given. The definitions have been produced by synthetizing ideas from theories from several fields of research. The class of affects is defined as a superclass of emotions and feelings. Affect is defined as a process, in which a change in an agent's expected utility causes a bodily change. If the process is currently under the attention of the agent (i.e. the agent is conscious of it), the process is a feeling. If it is not, but can in principle be taken into attention (i.e. it is preconscious), the process is an emotion. Thus, affects do not presuppose consciousness, but emotions and affects do. Affects directed at unexpected materialized (i.e. past) events are delight and fright. Delight is the consequence of an unexpected positive event and fright is the consequence of an unexpected negative event. Affects directed at expected materialized (i.e. past) events are happiness (expected positive event materialized), disappointment (expected positive event did not materialize), sadness (expected negative event materialized) and relief (expected negative event did not materialize). Affects directed at expected unrealized (i.e. future) events are fear and hope. Some other affects can be defined as directed towards originators of the events. The affect classification has also been implemented as a computer program, the purpose of which is to ensure the coherence of the definitions and also to illustrate the capabilities of the model. The exact content of bodily changes associated with specific affects is not considered relevant from the point of view of the logical structure of affective phenomena. The utility function need also not be defined, since the target of examination is only its dynamics.

The Nature, Origins, and Consequences of Finnish Shame-Proneness: A Grounded Theory Study

Although shame is a universal human emotion and is one of the most difficult emotions to overcome, its origins and nature as well as its effects on psychosocial functioning are not well understood or defined. While psychological and spiritual counselors are aware of the effects and consequences of shame for an individual s internal well-being and social life, shame is often still considered a taboo topic and is not given adequate attention. This study aims to explain the developmental process and effects of shame and shame-proneness for individuals and provide tools for practitioners to work more effectively with their clients who struggle with shame. This study presents the empirical foundation for a grounded theory that describes and explains the nature, origins, and consequences of shame-proneness. The study focused on Finnish participants childhood, adolescence and adulthood experiences and why they developed shame-proneness, what it meant for them as children and adolescents and what it meant for them as adults. The data collection phase of this study began in 2000. The participants were recruited through advertisements in local and country-wide newspapers and magazines. Altogether 325 people responded to the advertisements by sending an essay concerning their shame and guilt experiences. For the present study, 135 essays were selected and from those who sent an essay 19 were selected for in-depth interviews. In addition to essays and interviews, participants personal notebooks and childhood hospital and medical reports as well as their scores on the Internalized Shame Scale were analyzed. The development of shame-proneness and significant experiences and events during childhood and adolescence (e.g., health, parenting and parents behavior, humiliation, bullying, neglect, maltreatment and abuse) are discussed and the connections of shame-proneness to psychological concepts such as self-esteem, attachment, perfectionism, narcissism, submissiveness, pleasing others, heightened interpersonal subjectivity, and codependence are explained. Relationships and effects of shame-proneness on guilt, spirituality, temperament, coping strategies, defenses, personality formation and psychological health are also explicated. In addition, shame expressions and the development of shame triggers as well as internalized and externalized shame are clarified. These connections and developments are represented by the core category lack of gaining love, validation and protection as the authentic self. The conclusions drawn from the study include a categorization of shame-prone Finnish people according to their childhood and adolescent experiences and the characteristics of their shame-proneness and personality. Implications for psychological and spiritual counseling are also discussed. Key words: shame, internalized shame, external shame, shame development, shame triggers, guilt, self-esteem, attachment, narcissism, perfectionism, submissiveness, codependence, childhood neglect, childhood abuse, childhood maltreatment, emotional abuse, sexual abuse, spiritual abuse, psychological well-being

Pyhä Teresa ja keskiajan mystiikan teoriat

In my dissertation I have studied St Teresa (1515-1582) in the light of medieval mystical theories. I have two main levels in my research: historical and theological. On the historical level I study St Teresa s personal history in the context of her family and the Spanish society. On the theological level I study both St Teresa s mysticism and her religious experience in the light of medieval mysticism. St Teresa wrote a book called Life , which is her narrative autobiography and story about her mystical spiritual formation. She reflected herself through biblical texts interpreting them in the course of the biblical hermeneutics like allegory, typology, tropology and anagogy. In addition to that she read others life stories from her period of time, but reflected herself only slightly through the sociological point of view. She used irony as a means to gain acceptance to her authority and motive to write. Her position has been described as a double bind because of writing at the request of educated men and to the non-educated women as she herself was uneducated. She used irony as a means to achieve valuation to women, to gain negative attributes connected to them and to gain authority to teach them mystical spirituality, the Bible and prayer. In this ironic tendency she was a feminist writer. In order to understand medieval mysticism I have written in the first chapter a review of the main trends in medieval mysticism in connection with the classical emotional theories. Two medieval mystical theories show an important role in St Teresa s mysticism. One is love mysticism and the other is the three partite way of mysticism (purification, illumination and union). The classic-philosophical emotional theories play a role in both patterns. The theory of love mysticism St Teresa interpreted in the traditional way stressing the spiritual meaning of love in connexion with God and neighbors. Love is an emotion, which is bound with other emotions, but all objects of love don t strengthen spiritual love. In the three partite way of mysticism purification means to find biblical values in life and to practice meditative self-knowledge theologically interpreted. In illumination human understanding has to be illuminated by God and united to mystical knowledge from God. St Teresa considered illumination a way to learn things. Illumination has also psychological aspects like recognition of many trials and pains, which come from life on earth. Theologically interpreted in illumination one should die to oneself, let oneself be transformed and renewed by God. I have also written a review of the modern philosophical discussion on personal identity where memory and mental experiences are important creators of personal identity. St Teresa bound medieval mystical teaching together with her personal religious experience. Her personal identity is by its character based on her narrative life story where mental experiences play important role. Previous researchers have labelled St Teresa as an ecstatic person whose experiences produced ecstatic phenomena to the mysticism. These phenomena combined with visions have in one respect made of her a person who has brought physical and visionary tendencies to theology. In spite of that she also represents a modern tendency trying to give words to experiences, which at first seem to be exceptional and extreme and which are easily interpreted as one-sided either physical or sexual or unsaid. In other respect I have stressed the personality of St Teresa that was represented as both strong and weak. The strong personality for her is demonstrated by religious faith and in its practice. The weak personality was for her a natural personal identity. St Teresa saw a unifying aspect in almost all. Firstly, her mysticism was aimed towards union with God and secondly, the unifying aspects and common rules in human relations in community life were central. Union with God is based on the fact that in a soul God is living in its centre, where God is present in the Trinitarian way. The picture of God in ourselves is a mirror but to get to know God better is to recognize his/her presence in us. When the soul recognizes itself as a dwelling place of God, it knows itself as God knows him/herself. There is equality between God and the soul. To be a Christian means to participate in God in his Trinitarian being. The participation to God is a process of divinization that puts a person into transformation, change and renewal. The unitive aspect concludes also knowledge of opposites between experience of community and solitude as well as community and separateness. As a founder of monasteries St Teresa practiced theology of poverty. She renewed the monastic life founding a rule called discalced that stressed ascetic tendencies. Supporters of her work were after the difficulties in the beginning both society and churchly leaders. She wrote about the monasteries including in her description at times seriousness at times humor and irony. Her stories are said to be picaresque histories that contain stories of ordinary laymen and many unexpected occasions. She exercised a kind of Bakhtinian dialogue in her letters. St Teresa stressed the virtues like sacrifice, determination and courage in the monastic life. Most of what she taught of virtues is based on biblical spirituality but there are also psychological tendencies in her writings. The theological pedagogical advice is mixed with psychology, but she herself made no distinction between different aspects in her teaching. To understand St Teresa and her mysticism is to recognize that she mixes her personal religious experience and mysticism, which widens mysticism to religious experience in a new way, although this corresponds also the very definition of mysticism. St Teresa concentrated on mental-spiritual experiences and the aim of her mystical teaching was to produce a human mind well cured like a garden that has God as its gardener.

Essays in Philosophical Moral Psychology

The dissertation consists of four essays and a comprehensive introduction that discusses the topics, methods, and most prominent theories of philosophical moral psychology. I distinguish three main questions: What are the essential features of moral thinking? What are the psychological conditions of moral responsibility? And finally, what are the consequences of empirical facts about human nature to normative ethics? Each of the three last articles focuses on one of these issues. The first essay and part of the introduction are dedicated to methodological questions, in particular the relationship between empirical (social) psychology and philosophy. I reject recent attempts to understand the nature of morality on the basis of empirical research. One characteristic feature of moral thinking is its practical clout: if we regard an action as morally wrong, we either refrain from doing it even against our desires and interests, or else feel shame or guilt. Moral views seem to have a conceptual connection to motivation and emotions – roughly speaking, we can’t conceive of someone genuinely disapproving an action, but nonetheless doing it without any inner motivational conflict or regret. This conceptual thesis in moral psychology is called (judgment) internalism. It implies, among other things, that psychopaths cannot make moral judgments to the extent that they are incapable of corresponding motivation and emotion, even if they might say largely the words we would expect. Is internalism true? Recently, there has been an explosion of interest in so-called experimental philosophy, which is a methodological view according to which claims about conceptual truths that appeal to our intuitions should be tested by way of surveys presented to ordinary language users. One experimental result is that the majority of people are willing to grant that psychopaths make moral judgments, which challenges internalism. In the first article, ‘The Rise and Fall of Experimental Philosophy’, I argue that these results pose no real threat to internalism, since experimental philosophy is based on a too simple conception of the relationship between language use and concepts. Only the reactions of competent users in pragmatically neutral and otherwise conducive circumstances yield evidence about conceptual truths, and such robust intuitions remain inaccessible to surveys for reasons of principle. The epistemology of folk concepts must still be based on Socratic dialogue and critical reflection, whose character and authority I discuss at the end of the paper. The internal connection between moral judgment and motivation led many metaethicists in the past century to believe along Humean lines that judgment itself consists in a pro-attitude rather than a belief. This expressivist view, as it is called these days, has far-reaching consequences in metaethics. In the second essay I argue that perhaps the most sophisticated form of contemporary expressivism, Allan Gibbard’s norm-expressivism, according to which moral judgments are decisions or contingency plans, is implausible from the perspective of the theory of action. In certain circumstances it is possible to think that something is morally required of one without deciding to do so. Morality is not a matter of the will. Instead, I sketch on the basis of Robert Brandom’s inferentialist semantics a weak form of judgment internalism, according to which the content of moral judgment is determined by a commitment to a particular kind of practical reasoning. The last two essays in the dissertation emphasize the role of mutual recognition in the development and maintenance of responsible and autonomous moral agency. I defend a compatibilist view of autonomy, according to which agents who are unable to recognize right and wrong or act accordingly are not responsible for their actions – it is not fair to praise or blame them, since they lacked the relevant capacity to do otherwise. Conversely, autonomy demands an ability to recognize reasons and act on them. But as a long tradition in German moral philosophy whose best-known contemporary representative is Axel Honneth has it, both being aware of reasons and acting on them requires also the right sort of higher-order attitudes toward the self. Without self-respect and self-confidence we remain at the mercy of external pressures, even if we have the necessary normative competence. These attitudes toward the self, in turn, are formed through mutual recognition – we value ourselves when those who we value value us. Thus, standing in the right sort of relations of recognition is indirectly necessary for autonomy and moral responsibility. Recognition and valuing are concretely manifest in actions and institutions, whose practices make possible participation on an equal footing. Seeing this opens the way for a kind of normative social criticism that is grounded in the value of freedom and automomy, but is not limited to defending negative rights. It thus offers a new way to bridge the gap between liberalism and communitarianism.

GPRA and the asthma locus on chromosome 7p14-p15

The basis of this work was the identification of a genomic region on chromosome 7p14-p15 that strongly associated with asthma and high serum total immunoglobulin E in a Finnish founder population from Kainuu. Using a hierarchical genotyping approach the linkage region was narrowed down until an evolutionary collectively inherited 133-kb haplotype block was discovered. The results were confirmed in two independent data sets: Asthma families from Quebec and allergy families from North-Karelia. In all the three cohorts studied, single nucleotide polymorphisms tagging seven common gene variants (haplotypes) were identified. Over half of the asthma patients carried three evolutionary closely related susceptibility haplotypes as opposed to approximately one third of the healthy controls. The risk effects of the gene variants varied from 1.4 to 2.5. In the disease-associated region, there was one protein-coding gene named GPRA (G Protein-coupled Receptor for Asthma susceptibility also known as NPSR1) which displayed extensive alternative splicing. Only the two isoforms with distinct intracellular tail sequences, GPRA-A and -B, encoded a full-length G protein-coupled receptor with seven transmembrane regions. Using various techniques, we showed that GPRA is expressed in multiple mucosal surfaces including epithelial cells throughout the respiratory tract. GPRA-A has additional expression in respiratory smooth muscle cells. However, in bronchial biopsies with unknown haplotypes, GPRA-B was upregulated in airways of all patient samples in contrast to the lack of expression in controls. Further support for GPRA as a common mediator of inflammation was obtained from a mouse model of ovalbumin-induced inflammation, where metacholine-induced airway hyperresponsiveness correlated with elevated GPRA mRNA levels in the lung and increased GPRA immunostaining in pulmonary macrophages. A novel GPRA agonist, Neuropeptide S (NPS), stimulated phagocytosis of Esterichia coli bacteria in a mouse macrophage cell line indicating a role for GPRA in the removal of inhaled allergens. The suggested GPRA functions prompted us to study, whether GPRA haplotypes associate with respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in infants sharing clinical symptoms with asthma. According to the results, near-term RDS and asthma may also share the same susceptibility and protective GPRA haplotypes. As in asthma, GPRA-B isoform expression was induced in bronchial smooth muscle cells in RDS and BPD suggesting a role for GPRA in bronchial hyperresponsiveness. In conclusion, the results of the present study suggest that the dysregulation of the GPRA/NPS pathway may not only be limited to the individuals carrying the risk variants of the gene but is also involved in the regulation of immune functions of asthma.

The Culture of Women's Housework : A Case Study of Bihar, India

This study examines gendered housework in India, particularly in Bihar. The perspective adopted in the study was in part derived from the data but also from sociological literature published both in Western countries and in India. The primary attention is therefore paid to modern and traditional aspects in housework. The aim is not to compare Indian practices to those of Western societies, but rather to use Western studies as a fruitful reference point. In that light, Indian housework practices appear to be traditional. Consequently, traditions are given a more significant role than is usually the case in studies on gendered housework, particularly in Western countries. The study approaches the topic mainly from the socio-cultural perspective; this provides the best means to understand the persistence of traditional habits in India. To get a wide enough picture of the division of labour, three methods were applied in the study: detailed time-use data, questionnaire and theme interviews. The data were collected in 1988 in two districts of Bihar, one rural and the other urban. The different data complement each other well but also bring to light contradictory findings: on a general level Biharian people express surprisingly modern views on gender equality but when talking in more detail (theme interviews) the interviewees told about how traditional housework practices still were in 1988. In the analysis of the data set four principal themes are discussed. Responsibility is the concept by which the study aims at understanding the logic of the argumentation on which the persistence of traditional housework practices is grounded. Contrary to the Western style, Biharian respondents appealed not to the principle of choice but to their responsibility to do what has to be done. The power of tradition, the early socialization of children to the traditional division of labour and the elusive nature of modernity are all discussed separately. In addition to the principle of responsibility, housework was also seen as an expression of affection. This was connected to housework in general but also to traditional practices. The purity principle was the third element that made Biharian interviewees favour housework in general, but as in the case of affection it too was interwoven with traditional practices. It seems to be so that if housework is in general preferred, this leads to preferring the traditional division of labour, too. The same came out when examining economic imperatives. However, the arguments concerning them proved to be rational. In analysing them it became clear that the significance of traditions is also much dependent on the economics: as far as the average income in India is very low, the prevalence of traditional practices in housework will continue. However, to make this work, cultural arguments are required: their role is to mediate more smoothly the iron rules of the economy. Key words: family, gendered housework, division of labour, responsibility, family togetherness, emotion, economy of housework, modernity, traditionality

Emotional experience in psychotherapeutic interaction : Conversation analytical study on cognitive psychotherapy

The dissertation examines how emotional experiences are oriented to in the details of psychotherapeutic interaction. The data (57 audio recorded sessions) come from one therapist-patient dyad in cognitive psychotherapy. Conversation analysis is used as method. The dissertation consists of 4 original articles and a summary. The analyses explicate the therapist s practices of responding to the patient s affective expressions. Different types of affiliating responses are identified. It is shown that the affiliating responses are combined with, or build grounds for, more interpretive and challenging actions. The study also includes a case study of a session with strong misalignment between the therapist s and patient s orientations, showing how this misalignment is managed by the therapist. Moreover, through a longitudinal analysis of the transformation of a sequence type, the study suggests that therapeutic change processes can be located to sequential relations of actions. The practices found in this study are compared to earlier research on everyday talk and on medical encounters. It is suggested that in psychotherapeutic interaction, the generic norms of interaction considering affiliation and epistemic access, are modified for the purposes of therapeutic work. The study also shows that the practices of responding to emotional experience in psychotherapy can deviate from the everyday practices of affiliation. The results of the study are also discussed in terms of concepts arising from clinical theory. These include empathy, validation of emotion, therapeutic alliance, interpretation, challenging beliefs, and therapeutic change. The therapist s approach described in this study involves practical integration of different clinical theories. In general terms, the study suggests that in the details of interaction, psychotherapy recurrently performs a dual task of empathy and challenging in relation to the patient s ways of describing their experiences. Methodologically, the study discusses the problem of identifying actions in conversation analysis of psychotherapy and emotional interaction, and the possibility to apply conversation analysis in the study of therapeutic change.

The sources of moral motivation : studies on empathy, guilt, shame and values

The goals of this study were to analyze the forms of emotional tendencies that are likely to motivate moral behaviors, and to find correlates for these tendencies. In study 1, students narratives of their own guilt or shame experiences were analyzed. The results showed that pure shame was more likely to motivate avoidance than reparation, whereas guilt and combination of guilt and shame were likely to motivate reparation. However, all types of emotion could lead to chronic rumination if the person was not clearly responsible for the situation. In study 2, the relations of empathy with two measures of guilt were examined in a sample of 13- to 16-year-olds (N=113). Empathy was measured using Davis s IRI and guilt by Tangney s TOSCA and Hoffman s semi-projective story completion method that includes two different scenarios, guilt over cheating and guilt over inaction. Empathy correlated more strongly with both measures of guilt than the two measures correlated with each other. Hoffman s guilt over inaction was more strongly associated with empathy measures in girls than in boys, whereas for guilt over cheating the pattern was the opposite. Girls and boys who describe themselves as empathetic may emphasize different aspect of morality and feel guilty in different contexts. In study 3, cultural and gender differences in guilt and shame (TOSCA) and value priorities (the Schwartz Value Survey) were studied in samples of Finnish (N=156) and Peruvian (N=159) adolescents. Gender differences were found to be larger and more stereotypical among the Finns than among the Peruvians. Finnish girls were more prone to guilt and shame than boys were, whereas among the Peruvians there was no gender difference in guilt, and boys were more shame-prone than girls. The results support the view that psychological gender differences are largest individualistic societies. In study 4, the relations of value priorities to guilt, shame and empathy were examined in two samples, one of 15 19-year-old high school students (N = 207), and the other of military conscripts (N = 503). Guilt was, in both samples, positively related to valuing universalism, benevolence, tradition, and conformity, and negatively related to valuing power, hedonism, stimulation, and self-direction. The results for empathy were similar, but the relation to the openness conservation value dimension was weaker. Shame and personal distress were weakly related to values. In sum, shame without guilt and the TOSCA shame scale are tendencies that are unlikely to motivate moral behavior in Finnish cultural context. Guilt is likely to be connected to positive social behaviors, but excessive guilt can cause psychological problems. Moral emotional tendencies are related to culture, cultural conceptions of gender and to individual value priorities.

Finnish Business Repatriates' Coping Strategies

This thesis explores Finnish business repatriates’ coping strategies. Managing repatriation has been recognized as a demanding task for companies and an important issue in international human resource management. However, we still know relatively little about how repatriates respond to the demands of the return. This thesis addresses this problem by applying a process approach to coping with repatriation. The focus is on identifying repatriates’ coping strategies and the various forms of them. This study also aims to investigate what might influence the use of repatriates’ coping strategies and forms of coping. The background of this doctoral study is provided by earlier research that identified factors influencing repatriates’ adjustment, either positively or negatively. The empirical material of this doctoral thesis comprises twenty-two Phase I semi-structured interviews and ten Phase II follow-up interviews conducted for the purposes of verification. The main findings of the study are formulated as propositions. For instance, it was suggested that repatriates are likely to use different forms of problem-focused strategy more often than various forms of emotion-focused strategy. Moreover, they also are likely to use a larger range of problem-focused strategies than emotion-focused strategies. In addition, in contrast to specialists, repatriates occupying managerial positions are likely to use a greater number and a greater variety of different forms of problem-focused strategy than of emotion-focused strategy, especially in the context of preparing for their return and in different work role changes. This thesis contributes to research on repatriation, expatriation, coping and identifies implications for management.

A Continuation of the Happiness Success Story: Does Happiness Impact Service Quality?

A Continuation of the Happiness Success Story: Does Happiness Impact Service Quality? The effects of long-term happiness on various outcomes for the individual and society have been studied extensively in psychology but the concept has so far received limited research attention in marketing. Happiness is defined as a summary judgment of one’s life. Previous research has shown that happiness is a relatively stable perception of happiness in one’s life. Thus, happiness in this thesis is long-term and more global as a phenomenon than in the marketing literature, where happiness is commonly conceptualized as an emotion, feeling or momentary state of happiness. Although there is plenty of research on consumer affect and its impact on service responses, there are no studies on the effect of long-term happiness on service evaluation. As empirical evidence suggests that happy people perceive smaller and bigger events in life more positively than less happy people and that happy people are more prone to experience positive feelings and less of negative feelings it was hypothesized that happiness affects service quality directly but also indirectly through mood. Therefore, in this thesis, it was set out to explore if happiness affects customer-perceived service quality. A survey method was adopted to study the relationship between happiness, mood and service quality. Two studies were conducted with a total of 17 investigated services. Out of the 17 different investigated cases, happiness was found to positively affect service quality in only four cases. The results from the two studies also provide weak support for a positive relationship between mood and service quality. Out of the 17 cases, mood was found to positively affect service quality in only three cases and the results provide additional evidence for the stream of literature arguing that affect plays no or only a minimal role in service quality. Based on the collective results in this study, it can be concluded that the evidence for a positive relationship between happiness, mood and service quality is weak. However, in this thesis, it was recognized that the happiness concept is relevant for marketers and serve potential to explain marketing related phenomena. Marketing researchers who are interested in studying happiness are advised to focus research attention on consumer well-being.

Myotonic dystrophy type 2 (DM2) : Diagnostic methods and molecular pathology

Myotonic dystrophies type 1 (DM1) and type 2 (DM2) are the most common forms of muscular dystrophy affecting adults. They are autosomal dominant diseases caused by microsatellite tri- or tetranucleotide repeat expansion mutations in transcribed but not translated gene regions. The mutant RNA accumulates in nuclei disturbing the expression of several genes. The more recently identified DM2 disease is less well known, yet more than 300 patients have been confirmed in Finland thus far, and the true number is believed to be much higher. DM1 and DM2 share some features in general clinical presentation and molecular pathology, yet they show distinctive differences, including disease severity and differential muscle and fiber type involvement. However, the molecular differences underlying DM1 and DM2 muscle pathology are not well understood. Although the primary tissue affected is muscle, both DMs show a multisystemic phenotype due to wide expression of the mutation-carrying genes. DM2 is particularly intriguing, as it shows an incredibly wide spectrum of clinical manifestations. For this reason, it constitutes a real diagnostic challenge. The core symptoms in DM2 include proximal muscle weakness, muscle pain, myotonia, cataracts, cardiac conduction defects and endocrinological disturbations; however, none of these is mandatory for the disease. Myalgic pains may be the most disabling symptom for decades, sometimes leading to incapacity for work. In addition, DM2 may cause major socio-economical consequences for the patient, if not diagnosed, due to misunderstanding and false stigmatization. In this thesis work, we have (I) improved DM2 differential diagnostics based on muscle biopsy, and (II) described abnormalities in mRNA and protein expression in DM1 and DM2 patient skeletal muscles, showing partial differences between the two diseases, which may contribute to muscle pathology in these diseases. This is the first description of histopathological differences between DM1 and DM2, which can be used in differential diagnostics. Two novel high-resolution applications of in situ -hybridization have been described, which can be used for direct visualization of the DM2 mutation in muscle biopsy sections, or mutation size determination on extended DNA-fibers. By measuring protein and mRNA expression in the samples, differential changes in expression patterns affecting contractile proteins, other structural proteins and calcium handling proteins in DM2 compared to DM1 were found. The dysregulation at mRNA level was caused by altered transciption and abnormal splicing. The findings reported here indicate that the extent of aberrant splicing is higher in DM2 compared to DM1. In addition, the described abnormalities to some extent correlate to the differences in fiber type involvement in the two disorders.

Molecular features of colorectal cancer predisposition and progression

Both inherited genetic variations and somatically acquired mutations drive cancer development. The aim of this thesis was to gain insight into the molecular mechanisms underlying colorectal cancer (CRC) predisposition and tumor progression. Whereas one-third of CRC may develop in the context of hereditary predisposition, the known highly penetrant syndromes only explain a small fraction of all cases. Genome-wide association studies have shown that ten common single nucleotide polymorphisms (SNPs) modestly predispose to CRC. Our population-based sample series of around thousand CRC cases and healthy controls was genotyped for these SNPs. Tumors of heterozygous patients were analyzed for allelic imbalance, in an attempt to reveal the role of these SNPs in somatic tumor progression. The risk allele of rs6983267 at 8q24 was favored in the tumors significantly more often than the neutral allele, indicating that this germline variant is somatically selected for. No imbalance targeting the risk allele was observed in the remaining loci, suggesting that most of the low-penetrance CRC SNPs mainly play a role in the early stages of the neoplastic process. The ten SNPs were further analyzed in 788 CRC cases, 97 of which had a family history of CRC, to evaluate their combined contribution. A significant association appeared between the overall number of risk alleles and familial CRC and these ten SNPs seem to explain around 9% of the familial clustering of CRC. Finding more CRC susceptibility alleles may facilitate individualized risk prediction and cancer prevention in the future. Microsatellite instability (MSI), resulting from defective mismatch repair function, is a hallmark of Lynch syndrome and observed in a subset of all CRCs. Our aim was to identify microsatellite frameshift mutations that inactivate tumor suppressor genes in MSI CRCs. By sequencing microsatellite repeats of underexpressed genes we found six novel MSI target genes that were frequently mutated in 100 MSI CRCs: 51% in GLYR1, 47% in ABCC5, 43% in WDTC1, 33% in ROCK1, 30% in OR51E2, and 28% in TCEB3. Immunohistochemical staining of GLYR1 revealed defective protein expression in homozygously mutated tumors, providing further support for the loss of function hypothesis. Another mutation screening effort sought to identify MSI target genes with putative oncogenic functions. Microsatellites were similarly sequenced in genes that were overexpressed and, upon mutation, predicted to avoid nonsense-mediated mRNA decay. The mitotic checkpoint kinase TTK harbored protein-elongating mutations in 59% of MSI CRCs and the mutant protein was detected in heterozygous MSI CRC cells. No checkpoint dysregulation or defective protein localization was observable however, and the biological relevance of this mutation may hence be related to other mechanisms. In conclusion, these two large-scale and unbiased efforts identified frequently mutated genes that are likely to contribute to the development of this cancer type and may be utilized in developing diagnostic and therapeutic applications.

Psychologically-Based and Content-Oriented Experience in Entertainment Virtual Environments

In daily life, rich experiences evolve in every environmental and social interaction. Because experience has a strong impact on how people behave, scholars in different fields are interested in understanding what constitutes an experience. Yet even if interest in conscious experience is on the increase, there is no consensus on how such experience should be studied. Whatever approach is taken, the subjective and psychologically multidimensional nature of experience should be respected. This study endeavours to understand and evaluate conscious experiences. First I intro-duce a theoretical approach to psychologically-based and content-oriented experience. In the experiential cycle presented here, classical psychology and orienting-environmental content are connected. This generic approach is applicable to any human-environment interaction. Here I apply the approach to entertainment virtual environments (VEs) such as digital games and develop a framework with the potential for studying experiences in VEs. The development of the methodological framework included subjective and objective data from experiences in the Cave Automatic Virtual Environment (CAVE) and with numerous digital games (N=2,414). The final framework consisted of fifteen factor-analytically formed subcomponents of the sense of presence, involvement and flow. Together, these show the multidimensional experiential profile of VEs. The results present general experiential laws of VEs and show that the interface of a VE is related to (physical) presence, which psychologically means attention, perception and the cognitively evaluated realness and spatiality of the VE. The narrative of the VE elicits (social) presence and involvement and affects emotional outcomes. Psychologically, these outcomes are related to social cognition, motivation and emotion. The mechanics of a VE affect the cognitive evaluations and emotional outcomes related to flow. In addition, at the very least, user background, prior experience and use context affect the experiential variation. VEs are part of many peoples lives and many different outcomes are related to them, such as enjoyment, learning and addiction, depending on who is making the evalua-tion. This makes VEs societally important and psychologically fruitful to study. The approach and framework presented here contribute to our understanding of experiences in general and VEs in particular. The research can provide VE developers with a state-of-the art method (www.eveqgp.fi) that can be utilized whenever new product and service concepts are designed, prototyped and tested.

Kiinnostusta vai ahdistusta? : Opettajaksi opiskelevien akateemiset tunteet, motivaatio ja opiskelun ongelmat suhteessa hyvinvointiin ja menestykseen aktivoivalla luentokurssilla

Previous studies indicate that positive learning experiences are related to academic achievement as well as to well-being. On the other hand, emotional and motivational problems in studying may pose a risk for both academic achievement and well-being. Thus, emotions and motivation have an increasing role in explaining university students learning and studying. The relations between emotions, motivation, study success and well-being have been less frequently studied. The aim of this study was to investigate what kind of academic emotions, motivational factors and problems in studying students experienced five days before an exam of an activating lecture course, and the relations among these factors as well as their relation to self-study time and study success. Furthermore, the effect of all these factors on well-being, flow experience and academic achievement was examined. The term academic emotion was defined as emotion experienced in academic settings and related to studying. In the present study the theoretical background to motivational factors was based on thinking strategies and attributions, flow experience and task value. Problems in studying were measured in terms of exhaustion, anxiety, stress, lack of interest, lack of self-regulation and procrastination. The data were collected in December 2009 in an activating educational psychology lecture course by using a questionnaire. The participants (n=107) were class and kindergarten teacher students from the University of Helsinki. Most of them were first year students. The course grades were also gathered. Correlations and stepwise regression analysis were carried out to find out the factors that were related to or explained study success. The clusters that presented students´ problems in studying as well as thinking strategies and attributions, were found through hierarchical cluster analysis. K-means cluster analysis was used to form the final groups. One-way analysis of variance, Kruskal-Wallis test and crosstabs were conducted to see whether the students in different clusters varied in terms of study success, academic emotions, task value, flow, and background variables. The results indicated that academic emotions measured five days before the exam explained about 30 % of the variance of the course grade; exhaustion and interest positively, and anxiety negatively. In addition, interest as well as the self-study time best explained study success on the course. The participants were classified into three clusters according to their problems in studying as well as their thinking strategies and attributions: 1) ill-being, 2) carefree, and 3) committed and optimistic students. Ill-being students reported most negative emotions, achieved the worst grades, experienced anxiety rather than flow and were also the youngest. Carefree students, on the other hand, expressed the least negative emotions and spent the least time on self-studying, and like committed students, experienced flow. In addition, committed students reported positive emotions the most often and achieved the best grades on the course. In the future, more in-depth understanding how and why especially young first year students experience their studying hard is needed, because early state of the studies is shown to predict later study success.

Autoimmune Regulator (AIRE) in the Maintenance of Immunological Tolerance

Autoimmune regulator (AIRE) is the gene mutated in the human polyglandular autoimmune disease called Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) that belongs to the Finnish disease heritage. Murine Aire has been shown to be important in the generation of the T cell central tolerance in the thymus by promoting the expression of ectopic tissue-specific antigens in the thymic medulla. Aire is also involved in the thymus tissue organization during organogenesis. In addition to the thymus, AIRE/Aire is expressed in the secondary lymphoid organs. Accordingly, a role for AIRE/Aire in the maintenance of peripheral tolerance has been suggested. Peripheral tolerance involves mechanisms that suppress immune responses in secondary lymphoid organs. Regulatory T cells (Tregs) are an important suppressive T cell population mediating the peripheral tolerance. Tregs are generated in the thymus but also in the peripheral immune system T cells can acquire the Treg-phenotype. The aim of this study was to characterize Tregs in APECED patients and in the APECED mouse model (Aire-deficient mice). In the mouse model, it was possible to separate Aire expression in the thymus and in the secondary lymphoid organs. The relative importance of thymic and peripheral Aire expression in the maintenance of immunological tolerance was studied in an experimental model that was strongly biased towards autoimmunity, i.e. lymphopenia-induced proliferation (LIP) of lymphocytes. This experimental model was also utilised to study the behaviour of T cells with dual-specific T cell receptors (TCR) during the proliferation. The Treg phenotype was studied by flow cytometry and relative gene expression with real-time polymerase chain reaction. TCR repertoires of the Tregs isolated from APECED patients and healthy controls were also compared. The dual-specific TCRs were studied with the TCR repertoire analysis that was followed with sequencing of the chosen TCR genes in order to estimate changes in the dual-specific TCR diversity. The Treg function was tested with an in vitro suppression assay. The APECED patients had normal numbers of Tregs but the phenotype and suppressive functions of the Tregs were impaired. In order to separate Aire functions in the thymus from its yet unknown role in the secondary lymphoid organs, the phenomenon of LIP was utilised. In this setting, the lymphocytes that are adoptively transferred to a lymphopenic recipient proliferate to stimuli from self-originating antigens. This proliferation can result in autoimmunity if peripheral tolerance is not fully functional. When lymphocytes that had matured without Aire in the thymus were transferred to lymphopenic Aire-sufficient recipients, no clinical autoimmunity followed. The Aire-deficient donor-originating lymphocytes hyperproliferated, and other signs of immune dysregulation were also found in the recipients. Overt autoimmunity, however, was prevented by the Aire-deficient donor-originating Tregs that hyperproliferated in the recipients. Aire-deficient lymphopenic mice were used to study whether peripheral loss of Aire had an impact on the maintenance of peripheral tolerance. When normal lymphocytes were transferred to these Aire-deficient lymphopenic recipients, the majority of recipients developed a clinically symptomatic colitis. The colitis was confirmed also by histological analysis of the colon tissue sections. In the Aire-deficient lymphopenic recipients Tregs were proliferating significantly less than in the control group s recipients that had normal Aire expression in their secondary lymphoid organs. This study shows that Aire is not only important in the central tolerance but is also has a significant role in the maintenance of the peripheral tolerance both in mice and men. Aire expressed in the secondary lymphoid organs is involved in the functions of Tregs during an immune response. This peripheral expression appears to be relatively more important in some situations since only those lymphopenic recipients that had lost peripheral expression of Aire developed a symptomatic autoimmune disease. This AIRE-related Treg defect could be clinically important in understanding the pathogenesis of APECED.